Mechanism of Eliciting Antitumor Cell Immunity Via Lentivector Immunization

通过慢载体免疫引发抗肿瘤细胞免疫的机制

基本信息

  • 批准号:
    7759506
  • 负责人:
  • 金额:
    $ 27.93万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2007
  • 资助国家:
    美国
  • 起止时间:
    2007-04-01 至 2012-01-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Immunotherapy represents one of the most promising therapeutic modalities for cancer. However, the immune responses induced by current immunization approaches are generally insufficient to generate adequate clinical responses. Development of effective immunization approaches ultimately require rational designs based on detailed knowledge of how immune cells are activated. The antigen presenting function of DCs as whole population is well established, but the role of each distinct DC subset has not been defined but is critical for developing targeted effective immunization approaches. In this proposal we will focus our effort on understanding the roles of the different DC subsets in lentivector mediated genetic immunization and the mechanism of how T cell immune response is elicited. We hypothesize that cutaneous administration of lentivector will result in specific transduction of skin DCs (sDCs) and direct priming of naive T cells, which can exploited for designing more effective antitumor genetic immunization strategies. The specific Aims are as follows: Aim 1: To investigate the mechanism of T cell priming in lentivector immunization; Aim 2: To manipulate antigen processing pathways to elicit more effective T cell responses; and Aim 3: To evaluate the antitumor effectiveness of lentivector immunization. To accomplish these aims, DC subsets from lentivector immunized mice will be examined for their function of priming naive T cells ex vivo and in vivo. The mechanism of direct vs cross priming of naive T cells will be determined in vivo. In addition, the potential of utilizing lentivector immunization in inducing T cell immune responses against self tumor antigen will also be investigated. Promotion of endogenous antigen processing by ubiquitin mediated degradation pathway and exogenous antigen presentation by Fc receptor will be investigated to enhance T cell responses against melanoma self tumor Ag TRP-2. Our study will yield information pertinent to DC subsets that activate T cells in vivo, the mechanism how T cell are primed in vivo, and the potential of lentivector immunization in eliciting T cell responses against self tumor Ag. The knowledge gained from these studies will assist the design of more effective and safer genetic immunization approaches for antitumor immunotherapy.
描述(申请人提供):免疫疗法是最有前途的癌症治疗方法之一。然而,目前的免疫方法诱导的免疫反应一般不足以产生足够的临床反应。开发有效的免疫方法最终需要基于对免疫细胞如何激活的详细知识进行合理的设计。DC作为整个群体的抗原提呈功能已经得到很好的确立,但每个不同的DC亚群的作用尚未确定,但对于开发有针对性的有效免疫方法至关重要。在这项建议中,我们将集中精力了解不同的DC亚群在慢病毒载体介导的遗传免疫中的作用以及T细胞免疫应答的机制。我们假设,慢载体的皮肤给药将导致皮肤树突状细胞(SDCs)的特异性转导和初始T细胞的直接激发,这将被用于设计更有效的抗肿瘤基因免疫策略。其具体目的如下:目的1:探讨慢载体免疫中T细胞启动的机制;目的2:操纵抗原处理途径以诱导更有效的T细胞应答;目的3:评价慢载体免疫的抗肿瘤效果。为了达到这些目的,将检测慢载体免疫小鼠的DC亚群在体外和体内对初始T细胞的激活功能。初始T细胞的直接激发和交叉激发的机制将在体内确定。此外,还将探讨利用慢载体免疫来诱导针对自身肿瘤抗原的T细胞免疫反应的可能性。通过泛素介导的降解途径促进内源性抗原加工和Fc受体递呈外源性抗原,以增强T细胞对黑色素瘤自身瘤抗原Trp-2的应答。我们的研究将提供与体内激活T细胞的DC亚群相关的信息,T细胞在体内如何被启动的机制,以及慢载体免疫在诱导T细胞对自身肿瘤抗原的反应中的潜力。从这些研究中获得的知识将有助于设计更有效和更安全的抗肿瘤免疫治疗的基因免疫方法。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

YUKAI HE其他文献

YUKAI HE的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('YUKAI HE', 18)}}的其他基金

TCR engineering of human T cells for immunotherapy of hepatocellular carcinoma
人类 T 细胞的 TCR 工程用于肝细胞癌的免疫治疗
  • 批准号:
    10532224
  • 财政年份:
    2018
  • 资助金额:
    $ 27.93万
  • 项目类别:
TCR engineering of human T cells for immunotherapy of hepatocellular carcinoma
人类 T 细胞的 TCR 工程用于肝细胞癌的免疫治疗
  • 批准号:
    10063495
  • 财政年份:
    2018
  • 资助金额:
    $ 27.93万
  • 项目类别:
TCR engineering of human T cells for immunotherapy of hepatocellular carcinoma
人类 T 细胞的 TCR 工程用于肝细胞癌的免疫治疗
  • 批准号:
    10331001
  • 财政年份:
    2018
  • 资助金额:
    $ 27.93万
  • 项目类别:
Engineering alpha fetoprotein and glypican-3 to develop hepatoma (HCC) vaccines
改造甲胎蛋白和磷脂酰肌醇蛋白聚糖 3 以开发肝癌 (HCC) 疫苗
  • 批准号:
    8693488
  • 财政年份:
    2014
  • 资助金额:
    $ 27.93万
  • 项目类别:
Engineering alpha fetoprotein and glypican-3 to develop hepatoma (HCC) vaccines
改造甲胎蛋白和磷脂酰肌醇蛋白聚糖 3 以开发肝癌 (HCC) 疫苗
  • 批准号:
    9231438
  • 财政年份:
    2014
  • 资助金额:
    $ 27.93万
  • 项目类别:
Engineering alpha fetoprotein and glypican-3 to develop hepatoma (HCC) vaccines
改造甲胎蛋白和磷脂酰肌醇蛋白聚糖 3 以开发肝癌 (HCC) 疫苗
  • 批准号:
    8827287
  • 财政年份:
    2014
  • 资助金额:
    $ 27.93万
  • 项目类别:
Mechanism of Eliciting Antitumor Cell Immunity Via Lentivector Immunization
通过慢载体免疫引发抗肿瘤细胞免疫的机制
  • 批准号:
    7488736
  • 财政年份:
    2007
  • 资助金额:
    $ 27.93万
  • 项目类别:
Mechanism of Eliciting Antitumor Cell Immunity Via Lentivector Immunization
通过慢载体免疫引发抗肿瘤细胞免疫的机制
  • 批准号:
    7257540
  • 财政年份:
    2007
  • 资助金额:
    $ 27.93万
  • 项目类别:
Mechanism of Eliciting Antitumor Cell Immunity Via Lentivector Immunization
通过慢载体免疫引发抗肿瘤细胞免疫的机制
  • 批准号:
    7356416
  • 财政年份:
    2007
  • 资助金额:
    $ 27.93万
  • 项目类别:
Mechanism of Eliciting Antitumor Cell Immunity Via Lentivector Immunization
通过慢载体免疫引发抗肿瘤细胞免疫的机制
  • 批准号:
    7575681
  • 财政年份:
    2007
  • 资助金额:
    $ 27.93万
  • 项目类别:

相似国自然基金

Neo-antigens暴露对肾移植术后体液性排斥反应的影响及其机制研究
  • 批准号:
    2022J011295
  • 批准年份:
    2022
  • 资助金额:
    10.0 万元
  • 项目类别:
    省市级项目
结核分枝杆菌持续感染期抗原(latency antigens)的重组BCG疫苗研究
  • 批准号:
    30801055
  • 批准年份:
    2008
  • 资助金额:
    19.0 万元
  • 项目类别:
    青年科学基金项目

相似海外基金

A nanopore biosensor for leveling Mtb antigens in blood
用于平衡血液中 Mtb 抗原的纳米孔生物传感器
  • 批准号:
    10646134
  • 财政年份:
    2022
  • 资助金额:
    $ 27.93万
  • 项目类别:
Iptycene Coated Carbon Nanotube-Based Biosensors for the Detection of Blood Antigens
用于检测血液抗原的 Iptycene 涂层碳纳米管生物传感器
  • 批准号:
    542643-2019
  • 财政年份:
    2019
  • 资助金额:
    $ 27.93万
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Master's
Exploring the mechanism of bacterial glycosyltransferase BoGT6a to enable the interconversion of human blood group antigens.
探索细菌糖基转移酶 BoGT6a 实现人类血型抗原相互转化的机制。
  • 批准号:
    505040-2017
  • 财政年份:
    2019
  • 资助金额:
    $ 27.93万
  • 项目类别:
    Postgraduate Scholarships - Doctoral
How the ABO antigens acquire the expression on the red blood cells ?
ABO抗原如何在红细胞上表达?
  • 批准号:
    18K10137
  • 财政年份:
    2018
  • 资助金额:
    $ 27.93万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Exploring the mechanism of bacterial glycosyltransferase BoGT6a to enable the interconversion of human blood group antigens.
探索细菌糖基转移酶 BoGT6a 实现人类血型抗原相互转化的机制。
  • 批准号:
    505040-2017
  • 财政年份:
    2018
  • 资助金额:
    $ 27.93万
  • 项目类别:
    Postgraduate Scholarships - Doctoral
Large Scale systematic priorization of Plasmodium vivax blood stage vaccine antigens
间日疟原虫血期疫苗抗原的大规模系统优先级排序
  • 批准号:
    10219142
  • 财政年份:
    2018
  • 资助金额:
    $ 27.93万
  • 项目类别:
Exploring the mechanism of bacterial glycosyltransferase BoGT6a to enable the interconversion of human blood group antigens.
探索细菌糖基转移酶 BoGT6a 实现人类血型抗原相互转化的机制。
  • 批准号:
    505040-2017
  • 财政年份:
    2017
  • 资助金额:
    $ 27.93万
  • 项目类别:
    Postgraduate Scholarships - Doctoral
Molecular analysis and development of a DNA-testing method for erythrocyte blood group antigens
红细胞血型抗原 DNA 检测方法的分子分析和开发
  • 批准号:
    25450454
  • 财政年份:
    2013
  • 资助金额:
    $ 27.93万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Nanosystems in transplantation: blood group antigens as immunologic tolerogens for infant heart transplantation
移植中的纳米系统:血型抗原作为婴儿心脏移植的免疫耐受原
  • 批准号:
    350946-2008
  • 财政年份:
    2010
  • 资助金额:
    $ 27.93万
  • 项目类别:
    Collaborative Health Research Projects
Investigating the role of blood group antigens in campylobacter infections
研究血型抗原在弯曲杆菌感染中的作用
  • 批准号:
    G0901696/1
  • 财政年份:
    2010
  • 资助金额:
    $ 27.93万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了